By 2020, the expected number of cancer survivors in the US is projected to rise to 18.1 million individuals costing an estimated $158 billion US dollars. Radiation therapy currently plays an essential role in the management of nearly 60% of all cancer treatments. The success of radiotherapy depends on the ability to target malignant cells with radiation while simultaneously protecting surrounding healthy tissue from damaging effects. This is often challenged by respiratory-induced motion in the thoracic and abdominal regions during the delivery of the treatment. Our proposal addresses the current need for a cost-effective and non-invasive real- time motion management platform for radiotherapy that does not increase the dose burden to patients. We will develop and validate a novel image-guidance technique to directly track tumor motion using a 4D planar ultrasound transducer during radiation therapy that is coupled to a pre-treatment calibration training image set consisting of a simultaneous 4D ultrasound and 4D MRI acquisition. The image sets will be rapidly matched using advanced image and signal processing algorithms, allowing the display of virtual MR images of the tumor/organ motion in real-time from an ultrasound acquisition. Although our proposal focuses on radiation therapy of liver cancers, it is applicable to other areas of the body A multi-disciplinary team of researchers from University of Wisconsin (UW) and General Electric Global Research Center (GRC) covering expertise in ultrasound imaging and probe design, MRI, signal processing, radiation therapy physics and treatment planning. The completion of this work will result in several innovations including: a (2D) patch-like, MR and LINAC compatible 4D planar ultrasound transducer that is electronically steerable for hands-free operation to provide real-time virtual MR and ultrasound imaging for motion management during radiation therapy; a multi- modal tumor localization strategy that uses US and MRI; fast and accurate image processing algorithms that provide real-time information about the motion and location of tumor related soft-tissue structures within the patient; and, a novel image-guided radiation therapy motion management platform that will be used to guide treatments based on direct visualization of the moving tumor. The broad, long-term objective of this research is to demonstrate that our platform leads to improved clinical outcome in cancer patients by significantly increasing the therapeutic ratio between a moving tumor target volume and relevant sensitive structures Furthermore, the application of our proposal is not limited to IGRT, as the technology may be applied to other image-guided procedures (proton therapy, brachytherapy, biopsies, surgery, and drug delivery).